Access to Fluorazones by Intramolecular Dehydrative Cyclization of Aromatic Tertiary Amides: A Synthetic and Mechanistic Study

Béla Mátravölgyi, Tamás Hergert, Erika Bálint, Péter Bagi, F. Faigl

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

An efficient synthesis has been developed for the preparation of 9H-pyrrolo[1,2-a]indol-9-ones (fluorazones) from readily available anthranilic acid derivatives via a one-pot amide- and pyrrole-formation step, followed by an intramolecular cyclodehydration. The cyclodehydration process is mediated by the activation of aromatic tertiary amides by triflic anhydride (Tf2O). Comparison of various benzo-substituents is shown to demonstrate the high functional group tolerance of this transformation. In addition, study of the reaction mechanism is also presented to unfold the exact role of the applied base additive. Herein, as a first example, we report our findings that Tf2O-mediated amide activation is obstructed by the easy protonation of amides by the formed triflic acid during the activation step. Additionally, it has been also proven that the base additive is not involved in the transformation of O-triflyliminium triflates into reactive species (e.g., nitrilium triflates) and is only responsible to neutralize the superacid to avoid the protonation of both the secondary or tertiary amides.

Original languageEnglish
Pages (from-to)2282-2292
Number of pages11
JournalJournal of Organic Chemistry
Volume83
Issue number4
DOIs
Publication statusPublished - Feb 16 2018

Fingerprint

Cyclization
Amides
Chemical activation
Protonation
Pyrroles
Functional groups
Derivatives

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Access to Fluorazones by Intramolecular Dehydrative Cyclization of Aromatic Tertiary Amides : A Synthetic and Mechanistic Study. / Mátravölgyi, Béla; Hergert, Tamás; Bálint, Erika; Bagi, Péter; Faigl, F.

In: Journal of Organic Chemistry, Vol. 83, No. 4, 16.02.2018, p. 2282-2292.

Research output: Contribution to journalArticle

Mátravölgyi, Béla ; Hergert, Tamás ; Bálint, Erika ; Bagi, Péter ; Faigl, F. / Access to Fluorazones by Intramolecular Dehydrative Cyclization of Aromatic Tertiary Amides : A Synthetic and Mechanistic Study. In: Journal of Organic Chemistry. 2018 ; Vol. 83, No. 4. pp. 2282-2292.
@article{63d6432949334367ab581cf859534979,
title = "Access to Fluorazones by Intramolecular Dehydrative Cyclization of Aromatic Tertiary Amides: A Synthetic and Mechanistic Study",
abstract = "An efficient synthesis has been developed for the preparation of 9H-pyrrolo[1,2-a]indol-9-ones (fluorazones) from readily available anthranilic acid derivatives via a one-pot amide- and pyrrole-formation step, followed by an intramolecular cyclodehydration. The cyclodehydration process is mediated by the activation of aromatic tertiary amides by triflic anhydride (Tf2O). Comparison of various benzo-substituents is shown to demonstrate the high functional group tolerance of this transformation. In addition, study of the reaction mechanism is also presented to unfold the exact role of the applied base additive. Herein, as a first example, we report our findings that Tf2O-mediated amide activation is obstructed by the easy protonation of amides by the formed triflic acid during the activation step. Additionally, it has been also proven that the base additive is not involved in the transformation of O-triflyliminium triflates into reactive species (e.g., nitrilium triflates) and is only responsible to neutralize the superacid to avoid the protonation of both the secondary or tertiary amides.",
author = "B{\'e}la M{\'a}trav{\"o}lgyi and Tam{\'a}s Hergert and Erika B{\'a}lint and P{\'e}ter Bagi and F. Faigl",
year = "2018",
month = "2",
day = "16",
doi = "10.1021/acs.joc.7b03176",
language = "English",
volume = "83",
pages = "2282--2292",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "4",

}

TY - JOUR

T1 - Access to Fluorazones by Intramolecular Dehydrative Cyclization of Aromatic Tertiary Amides

T2 - A Synthetic and Mechanistic Study

AU - Mátravölgyi, Béla

AU - Hergert, Tamás

AU - Bálint, Erika

AU - Bagi, Péter

AU - Faigl, F.

PY - 2018/2/16

Y1 - 2018/2/16

N2 - An efficient synthesis has been developed for the preparation of 9H-pyrrolo[1,2-a]indol-9-ones (fluorazones) from readily available anthranilic acid derivatives via a one-pot amide- and pyrrole-formation step, followed by an intramolecular cyclodehydration. The cyclodehydration process is mediated by the activation of aromatic tertiary amides by triflic anhydride (Tf2O). Comparison of various benzo-substituents is shown to demonstrate the high functional group tolerance of this transformation. In addition, study of the reaction mechanism is also presented to unfold the exact role of the applied base additive. Herein, as a first example, we report our findings that Tf2O-mediated amide activation is obstructed by the easy protonation of amides by the formed triflic acid during the activation step. Additionally, it has been also proven that the base additive is not involved in the transformation of O-triflyliminium triflates into reactive species (e.g., nitrilium triflates) and is only responsible to neutralize the superacid to avoid the protonation of both the secondary or tertiary amides.

AB - An efficient synthesis has been developed for the preparation of 9H-pyrrolo[1,2-a]indol-9-ones (fluorazones) from readily available anthranilic acid derivatives via a one-pot amide- and pyrrole-formation step, followed by an intramolecular cyclodehydration. The cyclodehydration process is mediated by the activation of aromatic tertiary amides by triflic anhydride (Tf2O). Comparison of various benzo-substituents is shown to demonstrate the high functional group tolerance of this transformation. In addition, study of the reaction mechanism is also presented to unfold the exact role of the applied base additive. Herein, as a first example, we report our findings that Tf2O-mediated amide activation is obstructed by the easy protonation of amides by the formed triflic acid during the activation step. Additionally, it has been also proven that the base additive is not involved in the transformation of O-triflyliminium triflates into reactive species (e.g., nitrilium triflates) and is only responsible to neutralize the superacid to avoid the protonation of both the secondary or tertiary amides.

UR - http://www.scopus.com/inward/record.url?scp=85042198169&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042198169&partnerID=8YFLogxK

U2 - 10.1021/acs.joc.7b03176

DO - 10.1021/acs.joc.7b03176

M3 - Article

AN - SCOPUS:85042198169

VL - 83

SP - 2282

EP - 2292

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 4

ER -